OMIA:001505-9615 : Neuronal ceroid lipofuscinosis, 10 in Canis lupus familiaris (dog) |
In other species: sheep
Categories: Lysosomal storage disease , Nervous system phene
Links to possible relevant human trait(s) and/or gene(s) in OMIM: 610127 (trait) , 116840 (gene)
Links to relevant human diseases in MONDO:
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Disease-related: yes
Key variant known: yes
Year key variant first reported: 2006
Cross-species summary: One of several variants of neuronal ceroid lipofuscinosis (NCL) or Batten disease: CLN10; NCL10
Species-specific description: The neuronal ceroid lipofuscinoses (NCLs) are a group of lysosomal storage diseases characterized by intraneuronal accumulation of fluorescent granules and early neuronal death. Onset is usually before 2 years of age, with death by 7 years of age. Unlike other forms of NCL, dogs with NCL10 do not show signs of cerebral dysfunction or blindness. A genetic test is available.
Mapping: CFA18
Molecular basis: The causative variant is a c.597G>A transition in exon 5 of the CTSD gene leading to p.M199I in the encoded cathepsin D (Awano et al., 2006). Cathepsin D-specific activity in affected dogs is approximately 36% of normal.
Clinical features: Onset of signs is usually before 2 years of age and includes hypermetria, dysmetria, paraparesis, ataxia, and progressive psychomotor degeneration. Signs progress slowly, with death by 7 years of age (Awano et al., 2006).Unlike many other NCLs, American bulldogs with NCL10 do not show signs of cerebral dysfunction or blindness (Evans et al, 2005).
Pathology: Cytoplasmic autofluorescent storage material is present in neurons of the cerebrum, cerebellum, and retina. The most concentrated areas of neuronal cytoplasmic inclusion material is in the gracilic, medial, and lateral cuneate nuclei. Axonal spheroids indicative of neuroaxonal dystrophy are present in the thalamus, caudal medulla, and spinal cord grey matter. Muscle and nerve biopsies have changes consistent with mild denervation (Evans et al., 2005). In the retina, inclusions appear in photoreceptor cells, mostly in cones, in the outer limiting membrane next to the outermost layer of photoreceptor nuclei (Awano et al., 2006).
Prevalence: Allelic frequency was 28% in the American bulldog population studied to identify the causative mutation (Awano et al., 2006).
Control: Relatives of affected dogs should be tested. Avoid breeding affected or carrier dogs.
Genetic testing: A genetic test is available.
Breed:
American Bulldog (Dog) (VBO_0200034).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).
Associated gene:
| Symbol | Description | Species | Chr | Location | OMIA gene details page | Other Links |
|---|---|---|---|---|---|---|
| CTSD | cathepsin D | Canis lupus familiaris | 18 | NC_051822.1 (46700871..46691854) | CTSD | Homologene, Ensembl , NCBI gene |
Variants
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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
| OMIA Variant ID | Breed(s) | Variant Phenotype | Gene | Allele | Type of Variant | Source of Genetic Variant | Reference Sequence | Chr. | g. or m. | c. or n. | p. | Verbal Description | EVA ID | Year Published | PubMed ID(s) | Acknowledgements |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 66 | American Bulldog (Dog) | Neuronal ceroid lipofuscinosis, 10 | CTSD | missense | Naturally occurring variant | CanFam3.1 | 18 | g.46013354C>T | c.597G>A | p.(M199I) | 2006 | 16386934 | Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool |
Cite this entry
Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2013). OMIA:001505-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset]. https://omia.org/. https://doi.org/10.25910/2AMR-PV70
References
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
| 2023 | Cocostîrc, V., Paștiu, A.I., Pusta, D.L. : |
| An overview of canine inherited neurological disorders with known causal variants. Animals (Basel) 13:3568, 2023. Pubmed reference: 38003185. DOI: 10.3390/ani13223568. | |
| Stee, K., Van Poucke, M., Lowrie, M., Van Ham, L., Peelman, L., Olby, N., Bhatti, S.F.M. : | |
| Phenotypic and genetic aspects of hereditary ataxia in dogs. J Vet Intern Med 37:1306-1322, 2023. Pubmed reference: 37341581. DOI: 10.1111/jvim.16742. | |
| 2021 | Cerda-Gonzalez, S., Packer, R.A., Garosi, L., Lowrie, M., Mandigers, P.J.J., O'Brien, D.P., Volk, H.A. : |
| International veterinary canine dyskinesia task force ECVN consensus statement: Terminology and classification. J Vet Intern Med 35:1218-1230, 2021. Pubmed reference: 33769611. DOI: 10.1111/jvim.16108. | |
| 2020 | Story, B.D., Miller, M.E., Bradbury, A.M., Million, E.D., Duan, D., Taghian, T., Faissler, D., Fernau, D., Beecy, S.J., Gray-Edwards, H.L. : |
| Canine models of inherited musculoskeletal and neurodegenerative diseases. Front Vet Sci 7:80, 2020. Pubmed reference: 32219101. DOI: 10.3389/fvets.2020.00080. | |
| 2017 | Katz, M.L., Rustad, E., Robinson, G.O., Whiting, R.E.H., Student, J.T., Coates, J.R., Narfstrom, K. : |
| Canine neuronal ceroid lipofuscinoses: Promising models for preclinical testing of therapeutic interventions. Neurobiol Dis 108:277-87, 2017. Pubmed reference: 28860089. DOI: 10.1016/j.nbd.2017.08.017. | |
| 2013 | Bond, M., Holthaus, S.M., Tammen, I., Tear, G., Russell, C. : |
| Use of model organisms for the study of neuronal ceroid lipofuscinosis. Biochim Biophys Acta 1832:1842-65, 2013. Pubmed reference: 23338040. DOI: 10.1016/j.bbadis.2013.01.009. | |
| 2006 | Awano, T., Katz, ML., O'Brien, DP., Taylor, JF., Evans, J., Khan, S., Sohar, I., Lobel, P., Johnson, GS. : |
| A mutation in the cathepsin D gene (CTSD) in American Bulldogs with neuronal ceroid lipofuscinosis. Mol Genet Metab 87:341-8, 2006. Pubmed reference: 16386934. DOI: 10.1016/j.ymgme.2005.11.005. | |
| 2005 | Evans, J., Katz, ML., Levesque, D., Shelton, GD., de Lahunta, A., O'Brien, D. : |
| A variant form of neuronal ceroid lipofuscinosis in American bulldogs. J Vet Intern Med 19:44-51, 2005. Pubmed reference: 15715047. | |
| Wöhlke, A., Distl, O., Drögemüller, C. : | |
| The canine CTSD gene as a candidate for late-onset neuronal ceroid lipofuscinosis. Anim Genet 36:530-2, 2005. Pubmed reference: 16293139. DOI: 10.1111/j.1365-2052.2005.01375.x. |
Edit History
- Created by Frank Nicholas on 26 Oct 2010
- Changed by Vicki Meyers-Wallen on 18 Sep 2011
- Changed by Frank Nicholas on 12 Dec 2011
- Changed by Tosso Leeb on 28 May 2013